Autor: |
Shuo Wan, Yadong Sun, Jiamin Fu, Hongrui Song, Zhiqiang Xiao, Quanli Yang, Sanfeng Wang, Gongwang Yu, Peiran Feng, Wenkai Lv, Liang Luo, Zerong Guan, Feng Liu, Qinghua Zhou, Zhinan Yin, Meixiang Yang |
Jazyk: |
angličtina |
Rok vydání: |
2022 |
Předmět: |
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Zdroj: |
Cell Death and Disease, Vol 13, Iss 10, Pp 1-14 (2022) |
Druh dokumentu: |
article |
ISSN: |
2041-4889 |
DOI: |
10.1038/s41419-022-05293-8 |
Popis: |
Abstract The mouse vaginal epithelium cyclically exhibits cell proliferation and differentiation in response to estrogen. Estrogen acts as an activator of mTOR signaling but its role in vaginal epithelial homeostasis is unknown. We analyzed reproductive tract-specific Rptor or Rictor conditional knockout mice to reveal the role of mTOR signaling in estrogen-dependent vaginal epithelial cell proliferation and differentiation. Loss of Rptor but not Rictor in the vagina resulted in an aberrant proliferation of epithelial cells and failure of keratinized differentiation. As gene expression analysis indicated, several estrogen-mediated genes, including Pgr and Ereg (EGF-like growth factor) were not induced by estrogen in Rptor cKO mouse vagina. Moreover, supplementation of EREG could activate the proliferation and survival of vaginal epithelial cells through YAP1 in the absence of Rptor. Thus, mTORC1 signaling integrates estrogen and growth factor signaling to mediate vaginal epithelial cell proliferation and differentiation, providing new insights into vaginal atrophy treatment for post-menopausal women. |
Databáze: |
Directory of Open Access Journals |
Externí odkaz: |
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